Adipose tissue sensitization to insulin induced by troglitazone and MEDICA 16 in obese Zucker rats in vivo

2003 ◽  
Vol 284 (4) ◽  
pp. E795-E803 ◽  
Author(s):  
Bella Kalderon ◽  
Nina Mayorek ◽  
Limor Ben-Yaacov ◽  
Jacob Bar-Tana
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Constant Infusion ◽  
Zucker Rats ◽  
Fasting State ◽  
Insulin Sensitizers ◽  
Adipose Tissue Lipolysis

The putative role played by insulin sensitizers in modulating adipose tissue lipolysis in the fasting state was evaluated in obese conscious Zucker rats treated with troglitazone or β,β′-tetramethylhexadecanedioic acid (MEDICA 16) and compared with nontreated lean and obese animals. The rates of appearance (Ra) of glycerol and free fatty acid (FFA), primary intra-adipose reesterification, and secondary reuptake of plasma FFA in adipose fat were measured using constant infusion of stable isotope-labeled [2H5]glycerol, [2,2-2H2]palmitate, and radioactive [3H]palmitate. The overall lipolytic flux (Raglycerol) was increased 1.7- and 1.4-fold in obese animals treated with troglitazone or MEDICA 16, respectively, resulting in increased FFA export (Ra FFA) in the troglitazone-treated rats. Primary intra-adipose reesterification of lipolysis-derived fatty acids was enhanced twofold by insulin sensitizers, whereas reesterification of plasma fatty acids was unaffected by either treatment. Despite the unchanged Ra FFA in MEDICA 16 or the increased Ra FFA induced by troglitazone, very low density lipoprotein production rates were robustly curtailed. Total adipose tissue reesterification, used as an estimate of glucose conversion to glyceride-glycerol, was increased 1.9-fold by treatment with the insulin sensitizers. Our results indicate that, in the fasting state, insulin sensitizers induce, in vivo, a significant activation rather than suppression of adipose tissue lipolysis together with stimulation of glucose conversion to glyceride-glycerol.

No effect of acute normobaric hypoxia on plasma triglyceride levels in fasting healthy men

2018 ◽  
Vol 43 (7) ◽  
pp. 727-732 ◽  
Author(s):  
Bimit Mahat ◽  
Étienne Chassé ◽  
Clare Lindon ◽  
Jean-François Mauger ◽  
Pascal Imbeault
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
Acute Hypoxia ◽  
Density Lipoprotein ◽  
Ambient Air ◽  
Normobaric Hypoxia ◽  
Fasting State ◽  
Nonesterified Fatty Acids ◽  
Healthy Men ◽  
Adipose Tissue Lipolysis

Circulating fatty acids are a major systemic energy source in the fasting state as well as a determinant of hepatic triglycerides (TG)-rich very-low-density lipoprotein production. Upon acute hypoxia, sympathetic arousal induces adipose tissue lipolysis, resulting in an increase in circulating nonesterified fatty acids (NEFA). Animal studies suggest that TG clearance may also be strongly reduced under hypoxia, though this effect has been shown to be dependent on temperature. Whether the hypoxia-induced rise in blood fatty acid concentrations affects fasting TG levels in humans under thermoneutral conditions remains unknown. TG, NEFA, and glycerol levels were measured in fasted healthy young men (n = 10) exposed for 6 h to either normoxia (ambient air) or acute hypoxia (fraction of inspired oxygen = 0.12) in a randomized, crossover design. Participants were casually clothed and rested in front of a fan in an environmental chamber maintained at 28 °C during each trial. Under hypoxia, a significantly greater increase in NEFA occurred (condition × time interaction, p = 0.049) and glycerol levels tended to be higher (condition × time, p = 0.104), suggesting an increase in adipose tissue lipolysis. However, plasma TG levels did not change over time and did not differ between the normoxia and hypoxia conditions. In conclusion, acute exposure to normobaric hypoxia under thermoneutral condition in healthy men during fasting state increased lipolysis without affecting circulating TG.

scholarly journals Effects of an oral and intravenous fat load on adipose tissue and forearm lipid metabolism

1999 ◽  
Vol 276 (2) ◽  
pp. E241-E248 ◽  
Author(s):  
Kevin Evans ◽  
Mo L. Clark ◽  
Keith N. Frayn
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acids ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hormone Sensitive Lipase ◽  
Nonesterified Fatty Acid ◽  
Subcutaneous Adipose

We have studied the fate of lipoprotein lipase (LPL)-derived fatty acids by measuring arteriovenous differences across subcutaneous adipose tissue and skeletal muscle in vivo. Six subjects were fasted overnight and were then given 40 g of triacylglycerol either orally or as an intravenous infusion over 4 h. Intracellular lipolysis (hormone-sensitive lipase action; HSL) was suppressed after both oral and intravenous fat loads ( P < 0.001). Insulin, a major regulator of HSL activity, showed little change after either oral or intravenous fat load, suggesting that suppression of HSL action occurred independently of insulin. The rate of action of LPL (measured as triacylglycerol extraction) increased with both oral and intravenous fat loads in adipose tissue ( P = 0.002) and skeletal muscle ( P = 0.001). There was increased escape of LPL-derived fatty acids into the circulation from adipose tissue, shown by lack of reesterification of fatty acids. There was no release into the circulation of LPL-derived fatty acids from skeletal muscle. These results suggest that insulin is not essential for HSL suppression or increased triacylglycerol clearance but is important in reesterification of fatty acids in adipose tissue but not uptake by skeletal muscle, thus affecting fatty acid partitioning between adipose tissue and the circulation, postprandial nonesterified fatty acid concentrations, and hepatic very low density lipoprotein secretion.

Nascent and remnant lipoprotein turnover in rats: experimental design and simulation

1983 ◽  
Vol 245 (3) ◽  
pp. R386-R395
Author(s):  
N. Baker ◽  
H. J. Rostami ◽  
J. Elovson
Keyword(s):  
Fatty Acids ◽  
Molecular Weight ◽  
Simulation Analysis ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Kinetic Behavior ◽  
Turnover Rates ◽  
Apoprotein B ◽  
Hydrolysis Of

We have attempted to predict the kinetic behavior of the complex very low-density lipoprotein (VLDL; d less than 1.006) fraction in blood plasma of rats in the steady state. Specifically we proposed a simple model with two different kinds of nascent VLDL particles derived from the liver, one containing apoprotein B (PI/II) [apoB(PI/II)], the high-molecular-weight apoB, and the other, apoprotein B (PIII) [apoB(PIII)], the low-molecular-weight apoB. Two other particles, the corresponding remnants derived from the nascent VLDL particles were also included. Then a number of feasible in vivo tracer experiments were considered in which VLDL labeled in the apoB and/or triglyceride (TG) moieties would be injected into recipient rats and the kinetic behavior of the various compartments predicted by simulation analysis. In addition the kinetic behavior of products such as free fatty acids formed during hydrolysis of labeled TG fatty acids and liver TG derived from labeled circulating remnants was considered. Both the relative sizes of nascent and remnant particles and the extent of average hydrolysis of nascent VLDL-TG (before formation of a remnant particle) were considered in our analysis. On the basis of these predictions we have suggested a number of experimental approaches that should be helpful in defining the relative pool sizes and the turnover rates of each kind of particle in vivo.

scholarly journals Quantification in vivo of the effects of different types of dietary fat on the loci of control involved in hepatic triacylglycerol secretion

1995 ◽  
Vol 308 (2) ◽  
pp. 537-542 ◽  
Author(s):  
A M B Moir ◽  
B S Park ◽  
V A Zammit
Keyword(s):  
Fatty Acids ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Branch Points ◽  
Pharmacological Agents ◽  
Acid Diet ◽  
Fractional Rate ◽  
Selective Labelling ◽  
Hepatic Triacylglycerol

Polyunsaturated fatty acids (PUFA) have been suggested to exert their hypotriglyceridaemic effect through several possible mechanisms that would be expected to decrease the rate of hepatic very-low-density-lipoprotein-triacylglycerol secretion. We have quantified the role played in vivo by changes in the pattern of partitioning of (i) acyl-CoA between oxidation and esterification, (ii) diacylglycerol between synthesis of triacylglycerol and of the major phospholipids, and (iii) triacylglycerol between secretion and storage within the liver, in response to two dietary levels of n-6 and n-3 PUFA. In order to achieve this we used the technique of selective labelling of hepatic fatty acids in vivo. Compared with a predominantly saturated fatty acid diet, both n-6 and n-3 PUFA intake resulted in a decrease in the proportion of acyl moieties that were secreted by the liver, through an increased diversion of acyl-CoA towards oxidation and a lower fractional rate of secretion of newly synthesized triacylglycerol. In addition, a diet rich in n-3 fatty acids resulted not only in a greater magnitude of these effects but also in a doubling of the partitioning of diacylglycerol towards phospholipid labelling. It is shown that the overall 50% reduction achieved by fish oil feeding in the proportion of acyl groups that were secreted by the liver was distributed over all three branch points. The contribution of each of these adaptations was quantified. The application of such an approach, i.e. the localization and in vivo quantification of the importance of loci of control, in studies on dietary and pharmacological agents that affect lipaemia, is discussed.

Comparison of the effects of dietary n−3 and n−6 polyunsaturated fatty acids on very-low-density lipoprotein secretion when delivered to hepatocytes in chylomicron remnants

2001 ◽  
Vol 357 (2) ◽  
pp. 481-487 ◽  
Author(s):  
Xiaozhong ZHENG ◽  
Michael AVELLA ◽  
Kathleen M. BOTHAM
Keyword(s):  
Fatty Acids ◽  
Polyunsaturated Fatty Acids ◽  
Fish Oil ◽  
Corn Oil ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Chylomicron Remnants

The effects of chylomicron remnants enriched in n-3 or n-6 polyunsaturated fatty acids (derived from fish or corn oil respectively) on the secretion of very-low-density lipoprotein (VLDL) lipid and apolipoprotein B (apoB) by rat hepatocytes in culture was investigated. Remnants were prepared in vivo from chylomicrons obtained from rats given an oral dose of fish or corn oil and incubated with cultured hepatocytes for up to 16h. The medium was then removed and the secretion of cholesterol and triacylglycerol into the whole medium or the ρ < 1.050g/ml fraction during the following 7–24h was determined. After exposure of the cells to fish-oil as compared with corn-oil remnants, secretion of both cholesterol and triacylglycerol into the whole medium was decreased by 25–35%, and secretion into the ρ < 1.050g/ml fraction was decreased by 20–25%. In addition, the levels of apoB48 found in the ρ < 1.050g/ml fraction were significantly lower in cells treated with fish-oil rather than corn-oil remnants, although the levels of apoB100 remained unchanged. The expression of mRNA for apoB, as determined by reverse-transcriptase PCR, however, was not significantly changed after exposure of the cells to both types of remnants. These results demonstrate that the effects of dietary n-3 polyunsaturated fatty acids in depressing hepatic VLDL secretion occur directly when they are delivered to the liver from the intestine in chylomicron remnants, and that the secretion, but not the synthesis, of apoB is targeted.

scholarly journals Secretion and storage of newly synthesized hepatic triacylglycerol fatty acids in vivo in different nutritional states and in diabetes

1988 ◽  
Vol 255 (3) ◽  
pp. 929-935 ◽  
Author(s):  
J M Duerden ◽  
G F Gibbons
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Diurnal Variation ◽  
Low Density Lipoprotein ◽  
Specific Radioactivity ◽  
Lipid Synthesis ◽  
Density Lipoprotein ◽  
Dark Phase ◽  
Light Phase

Hepatic lipid synthesis was measured in rats in vivo with 3H2O, and the appearance of label in triacylglycerol and its constituent fatty acid and glycerol moieties was determined. In rats treated with Triton WR1339, the amount of newly synthesized fatty acid secreted as very-low-density lipoprotein (VLDL) triacylglycerol was greater during the dark phase of the diurnal cycle than during the light phase (11.3 versus 4.8 mumol of 3H2O/3 h per g of liver respectively). However, the total mass of VLDL triacylglycerol secreted remained constant, as did the amount of label in the secreted triacylglycerol glycerol. Newly synthesized fatty acids comprised only a small proportion of the total VLDL triacylglycerol fatty acids (TGFA) at both times (dark phase, 7.7%; light phase, 2.4%). Starvation for 24 h resulted in a small increase in the secretion of VLDL triacylglycerol. However, the contribution from newly synthesized fatty acids was decreased. Similar effects were observed in streptozotocin-diabetic animals. During the light and dark phases of the cycle, similar quantities of newly synthesized TGFA entered the hepatic cytosol, and these amounts were much smaller than those secreted as VLDL triacylglycerol. The mass of cytosolic triacylglycerol showed a diurnal variation, with a greater concentration during the light phase than in the dark. In diabetes, the mass of triacylglycerol was increased in the cytosol, as was the incorporation of labelled acylglycerol glycerol. Diabetes also abolished the diurnal variation in the quantity of cytosolic triacylglycerol. In each group of animals the specific radioactivity of the microsomal triacylglycerol was similar to that of the respective newly secreted plasma VLDL. The specific radioactivity of the cytosolic triacylglycerol was only 15.8% (dark phase) or 16.8% (light phase) that of the microsomal triacylglycerol. This increased to 35.5% in the starved animals and 40.2% in the diabetic animals.

scholarly journals Differences in partitioning of meal fatty acids into blood lipid fractions: a comparison of linoleate, oleate, and palmitate

2009 ◽  
Vol 296 (1) ◽  
pp. E64-E71 ◽  
Author(s):  
Leanne Hodson ◽  
Siobhán E. McQuaid ◽  
Fredrik Karpe ◽  
Keith N. Frayn ◽  
Barbara A. Fielding
Keyword(s):  
Fatty Acids ◽  
Test Meal ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Blood Lipid ◽  
Nonesterified Fatty Acid ◽  
Lipid Fractions ◽  
Functional Consequences ◽  
Single Meal

There has been much interest in the health effects of dietary fat, but few studies have comprehensively compared the acute metabolic fate of specific fatty acids in vivo. We hypothesized that different classes of fatty acids would be variably partitioned in metabolic pathways and that this would become evident over 24 h. We traced the fate of fatty acids using equal amounts of [U-13C]linoleate, [U-13C]oleate, and [U-13C]palmitate given in a test breakfast meal in 12 healthy subjects. There was a tendency for differences in the concentrations of the tracers in plasma chylomicron-triacylglycerol (TG) (oleate > palmitate > linoleate). This pattern remained in plasma nonesterified fatty acid (NEFA) and very low-density lipoprotein (VLDL)-TG ( P ≤ 0.01 and P ≤ 0.02 for [U-13C]oleate vs. both [U-13C]palmitate and [U-13C]linoleate for NEFA and VLDL-TG, respectively). There was significantly more [U-13C]linoleate than the other two tracers in plasma cholesteryl ester and phospholipid (PL). Using the values for isotopic enrichment in the different lipid fractions compared with the test meal, we calculated the contribution of meal fatty acids to the respective fractions. At 24 h, 10% of plasma PL-linoleate originated from the breakfast test meal. This was significantly greater than for oleate and palmitate (both 3 ± 0.3%; P < 0.05). This pattern was also true for erythrocyte PL fatty acids. The marked rapid incorporation of linoleate from a single meal into blood PL fractions may have functional consequences such as maintenance of membrane fluidity and may explain why linoleate is a useful biomarker of dietary intake.

scholarly journals Peroxisome proliferator-activated receptor-γ regulates the expression and function of very-low-density lipoprotein receptor

2010 ◽  
Vol 298 (1) ◽  
pp. E68-E79 ◽  
Author(s):  
Huan Tao ◽  
Srikanth Aakula ◽  
Naji N. Abumrad ◽  
Tahar Hajri
Keyword(s):  
Adipose Tissue ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Low Density Lipoprotein Receptor ◽  
Density Lipoprotein Receptor ◽  
And Function

Very-low-density lipoprotein receptor (VLDLR) is a member of the low-density receptor family, highly expressed in adipose tissue, heart, and skeletal muscle. It binds apolipoprotein E-triglyceride-rich lipoproteins and plays a significant role in triglyceride metabolism. PPARγ is a primary regulator of lipid metabolism in adipocytes and controls the expression of an array of genes involved in lipid trafficking in adipocytes. However, it is not known whether VLDLR is also under the control of PPARγ. In this study, we investigated the role of PPARγ in the regulation of VLDLR expression and function in vivo and in vitro. During the differentiation of 3T3-L1 preadipocytes, the levels of VLDLR protein and mRNA increased in parallel with the induction of PPARγ expression and reached maximum in mature adipocytes. Treatment of differentiated adipocytes with PPARγ agonist pioglitazone upregulated VLDLR expression in dose- and time-dependent manners. In contrast, specific inhibition of PPARγ significantly downregulated the protein level of VLDLR. Induction of VLDLR is also demonstrated in vivo in adipose tissue of wild-type (WT) mice treated with pioglitazone. In addition, pioglitazone increased plasma triglyceride-rich lipoprotein clearance and increased epididymal fat mass in WT mice but failed to induce similar effects in vldlr−/−mice. These results were further corroborated by the finding that pioglitazone treatment enhanced adipogenesis and lipid deposition in preadipocytes of WT mice, while its effect in VLDLR-null preadipocytes was significantly blunted. These findings provide direct evidence that VLDLR expression is regulated by PPARγ and contributes in lipid uptake and adipogenesis.

scholarly journals No effect of 10 weeks erythropoietin treatment on lipid oxidation in healthy men

2020 ◽  
Vol 9 (12) ◽  
pp. 1148-1155
Author(s):  
Jeyanthini Risikesan ◽  
Birgitte Nellemann ◽  
Britt Christensen ◽  
Jens Otto Lunde Jørgensen ◽  
Søren Nielsen
Keyword(s):  
Fatty Acids ◽  
Lipid Oxidation ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Resting Energy Expenditure ◽  
Oxidation Rates ◽  
Relative Contribution ◽  
The Impact

Studies indicate that erythropoietin (EPO) has effect on lipid and energy metabolism; however, the impact of EPO on lipid oxidation in vivo has not been well documented. Here, we evaluate whether long-term erythropoiesis-stimulating agent (ESA) treatment affects the oxidation of plasma very low-density lipoprotein triglycerides (VLDL-TG) fatty acids (FA), plasma free fatty acids (FFA) and non-plasma (residual) FA in healthy, young, sedentary men. Infusion of [1-14C]VLDL-TG and [9,10-3H]palmitate was used in combination with indirect calorimetry to assess resting lipid fuel utilization and kinetics, and resting energy expenditure (REE) before and after 10 weeks of ESA exposure compared with placebo. REE increased significantly during ESA compared with placebo (P = 0.023, RM-ANOVA). Oxidation rates of VLDL-TG FA, FFA, and residual FA remained unchanged during ESA compared with placebo. The relative contribution of the lipid stores was greatest for FFA (47.1%) and the total lipid oxidation rate and was not significantly different between ESA and placebo-treated subjects. We conclude that long-term ESA treatment of healthy young men increases REE but does not alter the oxidation rates of plasma and non-plasma FA sources.

Triglyceride kinetics, tissue lipoprotein lipase, and liver lipogenesis in septic rats

1990 ◽  
Vol 258 (4) ◽  
pp. E678-E685 ◽  
Author(s):  
S. Lanza-Jacoby ◽  
A. Tabares
Keyword(s):  
Adipose Tissue ◽  
Lipoprotein Lipase ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
E Coli ◽  
Inbred Rats ◽  
Peripheral Clearance ◽  
Vldl Triglyceride ◽  
Kinetics Of

The mechanism for the development of hypertriglyceridemia during gram-negative sepsis was studied by examining liver production and clearance of very-low-density lipoprotein (VLDL) triglyceride (TG). To assess liver output and peripheral clearance the kinetics of VLDL-TG were determined by a constant iv infusion of [2-3H]glycerol-labeled VLDL. Clearance of VLDL-TG was also evaluated by measuring activities of lipoprotein lipase (LPL) in heart, soleus muscle, and adipose tissue from fasted control, fasted E. coli-treated, fed control, and fed E. coli-treated rats. Lewis inbred rats, 275-300 g, were made septic with 8 x 10(7) live E. coli colonies per 100 g body wt. Twenty-four hours after E. coli injection, serum TG, free fatty acids (FFA), and cholesterol of fasted E. coli-treated rats were elevated by 170, 76, and 16%, respectively. The elevation of serum TG may be attributed to the 67% decrease in clearance rate of VLDL-TG in fasted E. coli-treated rats compared with their fasted controls. The suppressed activities of LPL in adipose tissue, skeletal muscle, and heart were consistent with reduced clearance of TG. Secretion of VLDL-TG declined by 31% in livers of fasted E. coli-treated rats, which was accompanied by a twofold increase in the composition of liver TG. Rates of in vivo TG synthesis in livers of the fasted E. coli-treated rats were twofold higher than in those of fasted control rats. Decreased rate of TG appearance along with the increase in liver synthesis of TG contributed to the elevation of liver lipids in the fasted E. coli-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

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